Targeting cancer stem cell pathways for cancer therapy

Abstract

Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

PI3Kγ inhibition suppresses microglia/TAM accumulation in glioblastoma microenvironment to promote exceptional temozolomide response

“…We previously demonstrated that stochastic fluctuation in MYC expression influenced glioblastoma cell fate in terms of the equilibrium between entry and exit from the cancer stem cell states (63). Similar findings have been reported for other master-regulatory transcription factors in glioblastomas (64,73) and for other cancers (74,75). Our current study suggests that this equilibrium is influenced by glioblastoma microenvironmental factors, including microglia secretion of IL11.…”

DNA methylation patterns–based subtype distinction and identification of soft tissue sarcoma prognosis

“…Furthermore, the functional analysis discovered that these annotated genes were enriched in several biological processes and signaling pathways, like Cell adhesion process, apoptosis, SMAD pathway, phosphatidylinositol 3 − kinase (PI3K) pathway, intermediate filament cytoskeleton formation, and others. All of these biological processes and signaling pathway has been declared significantly correlated with tumorigenesis and progression [44][45][46]. These explores could provide clues to emphasize the relationship between these specific methylation sites and STSs biological processes and signaling pathways.…”

Low-dose Diosbulbin-B (DB) Regulates Tumor-Intrinsic PD-L1/NLRP3 Signaling Pathway to Increase Cisplatin-Sensitivity in Gastric Cancer (GC)

“…Cancer stem cells (CSCs) contributed to metastasis, recurrence and drug resistance in cancers [11][12][13][14], and previous data suggested that CSCs enrichment contributed to cisplatin-resistance in GC cells [17,18]. Therefore, elimination of CSCs will help to improve chemo-sensitivity in GC cells [19]. As expected, the present study found that CSCs tended to be enriched in CR-GC cells and acquired cisplatin-resistant GC (ACR-GC) cells, compared to their corresponding parental CS-GC cells, which were in keeping with the previous work [17,18] and re ected that continuous cisplatin pressure promote CSCs generation in GC cells.…”

“…In addition, recent data indicated that CSCs were pivotal for sustaining cisplatinresistance in multiple cancers, such as head and neck squamous cell carcinoma (HNSCC) [15], lung cancer [16] and GC [17,18]. Speci cally, Peng C et al found that restriction of CSCs features enhanced cisplatin sensitivity [17], and Zhang L et al validated that induction of CSCs properties increased cisplatin-resistance in GC cells [18], which suggested that elimination of CSCs was an ideal strategy to improve cisplatin-sensitivity in GC [19]. By conducting the preliminary experiments, we surprisingly found that low-dose DB regulated CSCs properties in GC cells, however, up until now, no existed literatures reported the link between DB and cell stemness.…”